A study of the effects of specific functional group reagents and affinity labeling reagents on the activity of purified catechol-O-methyl transferase (COMT) is being carried out. COMT is an enzyme which plays an important role in the metabolism of epinephrine and norepinephrine. This study is being undertaken in an attempt to elucidate the nature of the amino acid residues present at the active site of this enzyme and in an effort to determine the mechanism by which COMT catalyzes its transmethylation. Also of interest will be the purification and characterization of the soluble and membrane-bound forms of COMT preset in rat brain, liver and heart. The properties (kinetic, chemical, immunochemical) of these different forms of COMT are being examined in an effort to detect differences in their characteristics which could be used in the design of specific inhibitors. BIBLIOGRAPHIC REFERENCES: E.E. Smissman, J.R. Reid, D.A. Walsh and R.T. Borchardt, "Synthesis and Biological Activity of 2- and 4-Substituted-6,7-Dihydroxy-1,2,3,4-Tetrahydroisoquinolines", J. Med. Chem., 19, 127 (1976). R.T. Borchardt, E.E. Smissman, D. Nerland and J.R. Reid, "Catechol-O-Methyltransferase. 7. Affinity Labeling with the Oxidation Products of 6-Aminodopamine", J. Med. Chem., 19, 30 (1976).